先天性眼外肌纤维化一家系致病基因的连锁分析  

Linkage analysis for all known locus linked with congenital fibrosis of extraocular muscles in a Chinese family

作　　者：布娟[1] 董佳梅[2] 沈勤[3] 杜伟[1] 李静[1] 庞红蕾[1] 林淑芳[1] 王乐今[1] 

机构地区：[1]北京大学第三医院眼科,北京市100191 [2]北京大学第三医院中央党校院区,北京市100191 [3]上海交通大学附属第九人民医院眼科,上海市200011

出　　处：《眼科新进展》2011年第8期705-707,共3页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号:30950007)~~

摘　　要：目的分析一个中国人先天性眼外肌纤维化(congenital fibrosis of extraocularmuscles,CFEOM)家系的临床表型,并通过基因连锁分析的方法对该家系的致病基因进行定位研究。方法收集一个CFEOM家系,对家系所有成员进行详细的临床检查。确定其临床表型及遗传方式后,在位于11号染色体的已知CFEOM基因附近选取微卫星标记物进行连锁分析。运用MILINK软件计算最大优势对数LOD值。结果该家系的遗传方式为常染色体隐性遗传,家系中的5例患者均表现为典型的眼外肌纤维化特征。与该家系连锁的染色体微卫星标记物为D11S4151和D11S1320,其最大的LOD值为1.21。结论此家系为常染色体隐性遗传型CFEOM2型,其致病基因位于11号染色体的D11S4151和D11S1320之间,位于该区间内的已知基因PHOX2A/ARIX的突变可能是导致该家系致病的分子基础。Objective To describe the clinical phenotype in a Chinese family with congenital fibrosis of extraocular muscles（CFEOM） and determine the candidate gene using linkage analysis.Methods The detailed clinical ophthalmic examination was performed for all patients with CFEOM in a Chinese family.The genomic DNA of all family members was extracted from peripheral blood leukocytes.The family was tested for linkage analysis to known autosomal recessively CFEOM loci on chromosome 11q13（CFEOM2）.The microsatellite markers near known candidate gene were used as genetic markers.Two-point LOD scores were calculated using the LINKAGE program.Results The affected five members in the pedigree had classic phenotype of CFEOM.They were inherited as an autosomal recessive trait.The microsatellite markers were D11S4151 and D11S1320,the maximum LOD score was 1.21.Conclusion The disorder in this family should be referred as CFEOM2,the candidate gene locus on chromosome 11q13 between markers D11S4151 and D11S1320,the known candidate gene PHOX2A/ARIX mutation may be the molecular basis of pathopoiesis.

关 键 词：先天性眼外肌纤维化 常染色体隐性遗传 连锁分析 

分 类 号：R777.4[医药卫生—眼科]